Genetic Determinants of the Interventricular Septum Are Linked to Ventricular Septal Defects and Hypertrophic Cardiomyopathy.

Background: A large proportion of genetic risk remains unexplained for structural heart disease involving the interventricular septum (IVS) including hypertrophic cardiomyopathy and ventricular septal defects. This study sought to develop a reproducible proxy of IVS structure from standard medical imaging, discover novel genetic determinants of IVS structure, and relate these loci to diseases of the IVS, hypertrophic cardiomyopathy, and ventricular septal defect.

Methods: We estimated the cross-sectional area of the IVS from the 4-chamber view of cardiac magnetic resonance imaging in 32 219 individuals from the UK Biobank which was used as the basis of genome wide association studies and Mendelian randomization.

Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants.

The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci.

Robust estimates of heritable coronary disease risk in individuals with type 2 diabetes.

Type 2 diabetes (T2D) is an important heritable risk factor for coronary artery disease (CAD), the risk of both diseases being increased by metabolic syndrome (MS). With the availability of large-scale genome-wide association data, we aimed to elucidate the genetic burden of CAD risk in T2D predisposed individuals within the context of MS and their shared genetic architecture. Mendelian randomization (MR) analyses supported a causal relationship between T2D and CAD [odds ratio (OR) = 1.

Common genetic variants and modifiable risk factors underpin hypertrophic cardiomyopathy susceptibility and expressivity.

Hypertrophic cardiomyopathy (HCM) is a common, serious, genetic heart disorder. Rare pathogenic variants in sarcomere genes cause HCM, but with unexplained phenotypic heterogeneity. Moreover, most patients do not carry such variants.

Heritability and family-based GWAS analyses of the N-acyl ethanolamine and ceramide plasma lipidome.

Signalling lipids of the N-acyl ethanolamine (NAE) and ceramide (CER) classes have emerged as potential biomarkers of cardiovascular disease (CVD). We sought to establish the heritability of plasma NAEs (including the endocannabinoid anandamide) and CERs, to identify common DNA variants influencing the circulating concentrations of the heritable lipids, and assess causality of these lipids in CVD using 2-sample Mendelian randomization (2SMR). Nine NAEs and 16 CERs were analyzed in plasma samples from 999 members of 196 British Caucasian families, using targeted ultra-performance liquid chromatography with tandem mass spectrometry.